Insulin is a hormone produced in the pancreas which is essential for the proper metabolism of glucose in the blood. The failure to produce insulin in appropriate quantities results in the onset of diabetes mellitus.
Since the early 1900's diabetic conditions have been treated by periodic injections of insulin, coupled with diet and exercise control. It was initially felt that such treatment could be used to completely control a diabetic condition. It is difficult, however, to avoid over or under compensation since insulin injection generally cannot be timed to coincide with carbohydrate intake. Situations thus exist in which the amount of insulin present is either in excess of or less than that required to handle the specific blood glucose level at any given time. Such situations are especially severe when an individual with a diabetic condition is under stress conditions, such as surgery or during childbirth.
It is generally recognized that individuals do not respond uniformly to insulin treatments and that some patients are better managed by short acting (regular or Semilente) insulin which requires several injections per day, whereas other patients are better managed with intermediate (globin, NPH or Lente) or longer acting (protamine zinc or Ultralente) insulin which require less frequent injections. Neither the short nor the longer acting varieties of insulin is capable of regulating a patient's blood glucose concentration accurately on a minute-to-minute basis because of varying demands created by food and exercise. Only by following a life of balanced diet and exercise can a patient prevent sudden and excessive changes in the requirements for insulin. Such a regimen will maintain the patient's blood glucose concentration below an acceptable upper level, thereby limiting the possibility of hyperglycemia, and above a safe lower limit, thereby limiting the possibility of hypoglycemia. Unfortunately, a dangerously low blood glucose concentration can also result from the use of larger infusions of insulin to counteract a rising concentration of blood glucose. This is because there is an overshoot when the concentration of blood glucose ceases to increase or actually decreases and the presence of the insulin causes a rapid decline in blood glucose concentration to a concentration below the safe limit. The resulting hypoglycemia can be fatal in some cases.
Various systems and apparatus have been proposed to analyze the blood glucose concentration and to infuse insulin or glucose based upon such analysis in an effort to control the blood glucose level within desired ranges. One approach, referred to as the limit approach, continuously monitors a patient's blood glucose concentration and regulates this concentration by administering insulin when the concentration reaches an upper limit and administering dextrose when the blood glucose concentration reaches a lower limit. The limit approach, however, has several difficulties because it is possible to overshoot both the upper and lower limits. The system is not capable of controlling sudden changes in blood glucose concentration. Another approach is to use proportional regulation by solely matching the infusion rate of insulin to the blood glucose concentration according to a linear relationship. Here again, hypoglycemia can result if there is a large requirement for insulin followed by a natural reduction in the blood glucose concentration.
Still another approach is described in Diabetes 23(5), 389-404 (1974) in which apparatus is described having a computer which operates an infusion pump to infuse insulin or glucose based upon analytical blood glucose values. The computer derives its output signal for pump operation from algorithms based on hyperbolic tangential functions. While this prior art computer control has advantages, it also has the distinct disadvantage that the responses obtained do not always satisfactorily provide adequate control. In addition, the apparatus provides only limited flexibility in the selection of specific operating conditions for particular individuals whose blood glucose concentrations are being controlled by the apparatus.
The development of a rapid glucose analyzer with a total response time of less than two minutes has significantly affected the systems and apparatus being used. It is no longer necessary to calculate and use a predicted glucose value based on an averaging of previous glucose values, whether the average is an arithmetic mean or weighted average, in order to compensate for a long analyzer lag time because the response time of a rapid analyzer approximates the physiological response of a healthy subject. This fact has permitted improved apparatus for monitoring and controlling blood glucose levels to be developed.